Granzyme K CD8 T cells form a core population in inflamed human tissue
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ABSTRACT:
PROVIDER: PRJNA985379 | ENA |
REPOSITORIES: ENA
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Project description:Granzyme K CD8 T cells form a core population in inflamed human tissue
| PRJNA985378 | ENA
Project description: Not available
| S-EPMC9972878 | biostudies-literature
Project description:Cryopreserved synovial fluid mononuclear cells from three patients with seropositive rheumatoid arthritis were thawed and stained for surface antibodies, then fixed and stained for intracellular granzyme K and granzyme B. CD8 T cells with the following expression patterns were then isolated by FACS.
2022-05-08 | GSE202365 | GEO
Project description:Elucidating the true physiological functions of granzymes has been challenging since the origin of the granzyme studied, the use of non-physiological granzyme concentrations and the interspecies use of granzymes, with extrapolation of all these data to orthologous granzymes has led to inconsistencies. This is highly relevant for granzymes A and K where a debate is ongoing concerning their involvement in either cytotoxic or inflammatory processes, or in both. In order to tackle such contradictions, detailed knowledge of the substrate repertoires and substrate specificities of granzymes as well as their cleavage efficiencies may add in unraveling the primary signaling pathways these granzymes are involved in. Therefore, a degradome analysis using N-terminal COFRADIC was performed to unravel the substrate repertoires and subsite determinants for the closely related homologous human tryptases. We furthermore also profiled the uncharacterized mouse granzyme K in a comparative analysis with its human ortholog. Despite the subtle differences observed in the primary specificity profiles of these granzymes, for each granzyme distinguishing substrate subsite features could be elucidated.
2015-09-30 | PXD000570 | Pride
Project description:Bulk RNA-seq of human synovial fluid CD8 T cells sorted by Granzyme B vs Granzyme K expression
| PRJNA835733 | ENA
Project description:Neurodegenerative diseases trigger innate and adaptive immune responses that can either slow or accelerate disease progression. How immune cells contribute to such divergent disease outcomes is not entirely clear. Here, we sought to define beneficial immune pressure that emerged during development of tauopathies in mice and humans. Using mice that express mutant human tau in neurons, we observed that microglia slowed tauopathy development by controlling the spread of tau throughout the CNS and into the blood. However, over time microglia converted into distressed antigen presenting cells, acquired neuronal transcripts, and were targeted by resident CD8+ T cells. We detected clonally expanded CD8+ T cells in the CNS and draining lymph nodes of tauopathy mice that expressed granzyme K, but not traditional effector molecules (e.g., IFN, TNF, granzymes a/b/c), which was deposited onto the microglia they targeted. In fact, engagement of microglia by granzyme K expressing CD8+ T cells was a signature of tauopathy development in mice as well as humans with tau rich brain lesions linked to age, Alzheimer’s disease, or chronic traumatic encephalopathy. Deletion of CD8+ T cells in mice promoted the appearance of distressed microglia containing neuronal transcripts, markedly enhanced tau spread, and accelerated neurological decline. These data highlight a beneficial immune reaction involving microglia and granzyme K expressing CD8+ T cells that can slow tauopathy progression. Enhancement of this coordinated response offers the potential to improve outcomes in tauopathy patients.
2025-06-20 | GSE273753 | GEO
Project description:Neurodegenerative diseases trigger innate and adaptive immune responses that can either slow or accelerate disease progression. How immune cells contribute to such divergent disease outcomes is not entirely clear. Here, we sought to define beneficial immune pressure that emerged during development of tauopathies in mice and humans. Using mice that express mutant human tau in neurons, we observed that microglia slowed tauopathy development by controlling the spread of tau throughout the CNS and into the blood. However, over time microglia converted into distressed antigen presenting cells, acquired neuronal transcripts, and were targeted by resident CD8+ T cells. We detected clonally expanded CD8+ T cells in the CNS and draining lymph nodes of tauopathy mice that expressed granzyme K, but not traditional effector molecules (e.g., IFN, TNF, granzymes a/b/c), which was deposited onto the microglia they targeted. In fact, engagement of microglia by granzyme K expressing CD8+ T cells was a signature of tauopathy development in mice as well as humans with tau rich brain lesions linked to age, Alzheimer’s disease, or chronic traumatic encephalopathy. Deletion of CD8+ T cells in mice promoted the appearance of distressed microglia containing neuronal transcripts, markedly enhanced tau spread, and accelerated neurological decline. These data highlight a beneficial immune reaction involving microglia and granzyme K expressing CD8+ T cells that can slow tauopathy progression. Enhancement of this coordinated response offers the potential to improve outcomes in tauopathy patients.
2025-06-20 | GSE273752 | GEO
Project description:Neurodegenerative diseases trigger innate and adaptive immune responses that can either slow or accelerate disease progression. How immune cells contribute to such divergent disease outcomes is not entirely clear. Here, we sought to define beneficial immune pressure that emerged during development of tauopathies in mice and humans. Using mice that express mutant human tau in neurons, we observed that microglia slowed tauopathy development by controlling the spread of tau throughout the CNS and into the blood. However, over time microglia converted into distressed antigen presenting cells, acquired neuronal transcripts, and were targeted by resident CD8+ T cells. We detected clonally expanded CD8+ T cells in the CNS and draining lymph nodes of tauopathy mice that expressed granzyme K, but not traditional effector molecules (e.g., IFN, TNF, granzymes a/b/c), which was deposited onto the microglia they targeted. In fact, engagement of microglia by granzyme K expressing CD8+ T cells was a signature of tauopathy development in mice as well as humans with tau rich brain lesions linked to age, Alzheimer’s disease, or chronic traumatic encephalopathy. Deletion of CD8+ T cells in mice promoted the appearance of distressed microglia containing neuronal transcripts, markedly enhanced tau spread, and accelerated neurological decline. These data highlight a beneficial immune reaction involving microglia and granzyme K expressing CD8+ T cells that can slow tauopathy progression. Enhancement of this coordinated response offers the potential to improve outcomes in tauopathy patients.
2025-06-20 | GSE273757 | GEO
Project description:Patient-derived intestinal organoids provide an excellent tool to unravel mechanisms underlying ulcerative colitis (UC). Fresh biopsies, to isolate crypts and culture organoids, were obtained from both inflamed and non-inflamed regions from eight patients with active UC (Mayo endoscopic subscore ≥2), and from eight non-IBD controls.To address the inflammatory character of ex vivo organoids, we compared the transcriptome of biopsies, crypts and organoids derived from inflamed, and non-inflamed regions and aimed to (re-)induce inflammation ex vivo.
2020-10-08 | E-MTAB-7860 | biostudies-arrayexpress
Project description:Granzyme K+ CD8 T cells slow tauopathy progression by targeting microglia
| PRJNA1142965 | ENA